High miR-21 expression in breast cancer associated with poor disease-free survival in early stage disease and high TGF-β1

Abstract

is considered an oncomicroRNA given its abilities to suppress the actions of several tumor suppressor genes and to promote tumor cell growth, invasion and metastasis. Recently, transforming growth factor-beta (TGF-b) is found to up-regulate the expression of miR-21, and elevated miR-21 expression is seen frequently in breast cancer. To evaluate the effect of miR-21 on disease progression and its association with TGF-b, we analyzed miR-21 expression in breast cancer. Fresh tumor samples were collected during surgery from 344 patients diagnosed with primary breast cancer. The expression of miR-21 in tumor samples was measured with a TaqMan Ò microRNA assay using U6 as reference. Levels of miR-21 expression by disease stage, tumor grade, histology, hormone receptor status and lymph node involvement were compared. Cox proportional hazards regression analysis was performed to assess the association of miR-21 expression with disease-free and overall survival. The study results showed that the expression of miR-21 was detected in all tumor samples with substantial variation. High miR-21 expression was associated with features of aggressive disease, including high tumor grade, negative hormone receptor status, and ductal carcinoma. High miR-21 was also positively correlated with TGF-b1. No associations were found between patient survival and miR-21 expression among all patients, but high miR-21 was associated with poor disease-free survival in early stage patients (HR = 2.08, 95% CI: 1.08-4.00) despite no value for prognosis. The study supports the notion that miR-21 is an onco-microRNA for breast cancer. Elevated miR-21 expression may facilitate tumor progression, and TGF-b may up-regulate its expression.

Prognostic Importance of Single-Nucleotide Polymorphisms in IL-6, IL-10, TGF-β1, IFN-γ, and TNF-α Genes in Chronic Phase Chronic Myeloid Leukemia

“…Increased TGF-b1 expression and EGFR amplification accompany the emergence of highly aggressive human carcinomas. The literature contains data supporting the fact that the polymorphisms of this gene could be associated with susceptibility to the disease, but contrasting data in the literature suggest that such polymorphisms could be protective (Noori-Daloii et al, 2007;Castillego et al, 2009;Hawinkels et al, 2009;Qian et al, 2009). No associations were detected between TGF-b1 genotype/allele frequencies and CML in our study.…”

MicroRNAs and Breast Cancer

“…This study also reported a negative correlation with PTEN expression (p=0.013), a known downstream target of miR-21, in the same tissues [58]. The second study showed that high miR-21 expression was associated with features of aggressive disease, including high tumor grade, negative hormone receptor status, and ductal carcinoma, as well as a positive correlation with TGF-beta1 [59]. Although no association was found between patient survival and miR-21 expression among all patients, high miR-21 was associated with poor disease-free survival in early stage patients (HR = 2.08, 95% CI: 1.08-4.00) despite no value for prognosis.…”

Overexpression of miR-21 Promotes an In vitro Metastatic Phenotype by Targeting the Tumor Suppressor RHOB

“…Metastasis is generally associated with poor prognosis and, in some cancers, increased miR-21 expression (6,25,26). Therefore, identifying the role of miR-21 in invasion and migration can have direct clinical implications.…”